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Control of Synaptic Cargo Delivery by Microtubule End Resident Proteins.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Control of Synaptic Cargo Delivery by Microtubule End Resident Proteins./
作者:	Park, Jun Hyun.
面頁冊數:	1 online resource (160 pages)
附註:	Source: Dissertations Abstracts International, Volume: 85-01, Section: B.
Contained By:	Dissertations Abstracts International85-01B.
標題:	Neurosciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30309706click for full text (PQDT)
ISBN:	9798379781415

Control of Synaptic Cargo Delivery by Microtubule End Resident Proteins.
Park, Jun Hyun.

Control of Synaptic Cargo Delivery by Microtubule End Resident Proteins. - 1 online resource (160 pages)

Source: Dissertations Abstracts International, Volume: 85-01, Section: B.

Thesis (Ph.D.)--Yale University, 2023.

Includes bibliographical references

Neuron, a cell type that comprises the nervous system, requires unique polarized transport for its function. The neuronal polarity stems from the inherent biochemical asymmetry of the microtubule polymer which has GTP-bound tubulin enriched, dynamic plus end and more stable minus end on each pole. In most neurons, an axon has microtubule orientation where its plus end faces away from the cell body (plus-end out) while a dendrite has either mixed or plus end facing towards the cell body (minus-end out). Since microtubule orientation largely dictates the types of cargoes entering each neurite, microtubule polarity essentially defines the identity of neuronal subcompartments. Although how such gross microtubule polarity contributes to the neuronal identity have been studied extensively, the role of steady-state organization of microtubule and its binding proteins in neuronal function is less understood. In this thesis work, I have studied the role of microtubule end localizing proteins in sculpting precise synaptic connectivity and in biased loading of a single cargo to an axonal motor protein.In the first chapter, I will briefly summarize previous studies on polarized neuronal transports. Starting from selected works on kinesin motor proteins, I will connect these findings to more recent studies that show differential binding affinity of each kinesin motor to microtubules with post-translational modifications. Then I will discuss the role of microtubule associated proteins (MAPs) in biasing the motor walks. I will end this chapter with a perspective on how microtubule ends can regulate the cargo delivery.In the second chapter, I will present evidence on how a minus end localizing protein, VAB-8, regulates dynein mediated retrograde transport to define the length of en passant boutons of neuromuscular junction in C. elegans tail. In this work, we found immotile kinesin VAB-8 and Wnt signaling related protein PLR-1, when lost, locally disrupts the MT minus-end binding proteins on the synaptic microtubules. This specific loss of minus-end proteins resulted in synapse loss in the same region. We were able to show that the synapse loss is caused by hyperactive retrograde transport where hypomorphs of dynein could restore the lost synapses in these mutants.In the third chapter, I will present our finding that plus-end binding protein, EBP-1, is required for efficient transport of Dese Core Vesicles (DCV) in C. elegans neurons. ebp-1 knock-out animal exhibited DCV specific loss from the axon while sparing other cargoes such as Synaptic Vesicle Precursors (SVPs) and ATG-9 vesicles. Such observation was unexpected given all three tested cargoes are transported by the same motor protein, UNC-104, in C. elegans. I found evidence that endogenously labeled EBP-1 localized near subdomains of trans-Golgi region that has been implicated for DCV biogenesis. And Mammalian EB1, which can rescue the phenotype of ebp-1 KO worms, showed interaction with stalk region of KIF1A, the mammalian Kinesin-3. Collectively, EBP-1 biases the loading of DCV to Kinesin-3 by transiently recruiting Kinesin-3 to the site of DCV biogenesis. Loss of EBP-1, in turn, affects DCV trafficking specifically owing to the localization of EBP-1 in subdomains of Golgi.In the fourth chapter, I will discuss some remaining questions in the field of neuronal trafficking. And briefly discuss a unique case of asymmetric distribution of endoplasmic reticulum proteins in neurons and summarize a small-scale genetic screen I performed that identified mutants with neurite specific leakage of rough endoplasmic reticulum proteins.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798379781415Subjects--Topical Terms:

588700
Neurosciences.
Subjects--Index Terms:

Cargo deliveryIndex Terms--Genre/Form:

542853
Electronic books.

Control of Synaptic Cargo Delivery by Microtubule End Resident Proteins.
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